An examination of 16 million clinical documents representing 2.9 million patients also showed that patients who use a different type of antacid drug called an H2 blocker have no increased heart attack risk. The findings, reported in PLOS ONE, follow a Circulation report in 2013 in which scientists showed how — at a molecular level — PPIs might cause long-term cardiovascular disease and increase a patient’s heart attack risk.
“Our earlier work identified that the PPIs can adversely affect the endothelium, the Teflon-like lining of the blood vessels,” said John Cooke, M.D., Ph.D., a senior author of the PLOS ONE report. “That observation led us to hypothesize that anyone taking PPIs may be at greater risk for heart attack. Accordingly, in two large populations of patients, we asked what happened to people that were on PPIs versus other medications for the stomach.”
The PLOS ONE study’s principal investigator was Stanford vascular medicine specialist Nicholas J. Leeper, M.D.
In the present study, the researchers found a clear and significant association between exposure to PPIs and the occurrences of heart attack.
“By looking at data from people who were given PPI drugs primarily for acid reflux and had no prior history of heart disease, our data-mining pipeline signals an association with a higher rate of heart attacks,” said the PLOS ONE report’s lead author, Nigam H. Shah, Nigam H. Shah, M.B.B.S., Ph.D., an assistant professor of biomedical informatics at Stanford, where the work was done. “Our results demonstrate that PPIs appear to be associated with elevated risk of heart attack in the general population, and H2 blockers show no such association.”
The estimated increase of heart attack risk ranges from 16 to 21 percent, because of uncertainty in the estimation process, Shah said.
The FDA estimates about 1 in 14 Americans has used proton pump inhibitors. In 2009, PPIs were the third-most taken type of drug in the U.S., and are believed to account for $13 billion in annual global sales. Doctors prescribe PPIs to treat a wide range of disorders, including gastro-esophageal reflux disease, or GERD, infection by the ulcer-causing bacterium Helicobacter pylori, Zollinger-Ellison syndrome, and Barrett’s esophagus. The drugs can also be purchased over the counter. PPIs come in a variety of slightly different chemical forms, always ending with the suffix “-prazole,” for example, omeprazole or lansoprazole. Brand examples of PPIs are Nexium, Prilosec, and PrevAcid.
H2 blockers are another type of antacid drug. They are not believed to be associated with increased risk of heart attack or cardiovascular disease. Examples of the drug are cimetidine and ranitidine. Brand examples of H2 blockers are Zantac and Tagamet.
The researchers collected data from two repositories — STRIDE (Stanford Translational Research Integrated Database Environment), which contains information about 1.8 million Stanford hospital and clinic patients, and a subset of information for 1.1 million patients from the Web-based electronic medical records company Practice Fusion, Inc. Both sources of patient information were anonymized before the researchers accessed the data.
The group scanned the databases for patients who were prescribed proton pump inhibitors or other drugs, such as H2 blockers, and also looked to see if a given patient had a mention of having experienced a major cardiovascular event, such as myocardial infarction (heart attack), in their medical record.
Patients who had used PPIs were found to be at 1.16-1.21-fold-increased risk of heart attack.
A 2013 report to Circulation by several of the present report’s coauthors, including Cooke, raised the possibility that PPIs could lead to cardiovascular disease in the general population.
In the future, the researchers say they hope to conduct a large, prospective, randomized trial to determine whether PPIs are harmful to a broader population of patients.
To speak with Dr. John Cooke, please contact David Bricker, Houston Methodist, at 832-667-5811 or [email protected]. To speak with Drs. Shah and Leeper, please contact Bruce Goldman, Stanford University, at 650-725-2106 or [email protected].